title: Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers.
abstract: BACKGROUND
  Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery.
  
  
  OBJECTIVE
  To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability.
  
  
  METHODS
  Dry mixing techniques were employed to produce a small and fast dissolving buprenorphine/naloxone sublingual tablet formulation, OX219 (Zubsolv®), using sucralose and menthol as sweetener and flavor to mask the bitter taste of the active ingredients. Two cross-over studies were performed in healthy volunteers to evaluate pharmacokinetics, dissolve time and acceptability of OX219 5.7/1.4 mg tablets compared to the commercially available buprenorphine/naloxone formulations Suboxone® tablets and films (8/2 mg).
  
  
  RESULTS
  Buprenorphine exposure was equivalent in OX219 and Suboxone tablets. Sublingual dissolve times were significantly shorter for OX219 than for Suboxone tablets and were similar to Suboxone films. The OX219 formulation received significantly higher subjective ratings for taste and overall acceptability than both Suboxone formulations. OX219 was preferred over Suboxone tablet and film formulations by 77.4% and 88.9% of subjects, respectively.
  
  
  CONCLUSIONS
  A sublingual tablet formulation with an improved acceptability has been successfully developed.
authors.affiliation: Orexo AB , Uppsala , Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fischer
authors.forename: Martin
authors.initials: M
authors.lastname: Jönsson
authors.forename: Peter
authors.initials: P
authors.lastname: Hjelmström
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D002047:Buprenorphine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D000069479:Buprenorphine, Naloxone Drug Combination; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000069479:Buprenorphine, Naloxone Drug Combination; D004338:Drug Combinations; D009270:Naloxone; D002047:Buprenorphine
keywords: Absorption; Zubsolv; bioavailability; buprenorphine; dissolution; naloxone; taste masking; transmucosal drug delivery